The goal of our proposed research is to develop a Brucella vaccine that is safe for human use. Our approach has explored the use of live attenuated vaccines, since subunit vaccines have shown little real promise. Our approach combines the optimal features of a deliverable vaccine that is safe, free of side effects and efficacious in humans with enhanced immune stimulation through microencapsulation. The competitive advantages and innovations of our approach are: (1) use of a highly attenuated, safe, gene knockout, live B. melitensis mutants;(2) manufacturing with unique disposable closed system technologies, and (3) oral/intranasal delivery in a novel microencapsulation-mediated controlled release formula to optimally provide the long term mucosal immunostimulation required for protective immunity. Based upon our preliminary data, we postulate that our vaccine delivery system will ultimately be storage stable, administered orally or intranasally, and generally applicable to a number of select agents. We present a welldesigned 5-year timeline with milestones for developing GMP-produced vaccine for vaccination-aerosol challenge studies in non-human primates as a pathway to a clinical Investigational New Drug studies on the path to FDA Biological License Application. The development of the proposed product takes full advantage of a strong team and ongoing research with bacterial genetics and testing in multiple animal models coupled with novel manufacturing and microencapsulation technologies that balance product safety, stability, costs, and potency.